Mesoporous bioactive glass nanoparticles (MBGNs) have gained relevance in bone tissue engineering, especially since they can be used as vectors for therapeutically active ions like zinc (Zn) or copper (Cu). In this study, the osteogenic properties of the ionic dissolution products (IDPs) of undoped MBGNs (composition in mol%: 70 SiO₂, 30 CaO) and MBGNs doped with 5 mol% of either Zn (5Zn-MBGNs) or Cu (5Cu-MBGNs; compositions in mol%: 70 SiO₂, 25 CaO, 5 ZnO/CuO) on human bone marrow-derived mesenchymal stromal cells were evaluated. Extracellular matrix (ECM) formation and calcification were assessed, as well as the IDPs’ influence on viability, cellular osteogenic differentiation and the expression of genes encoding for relevant members of the ECM. The IDPs of undoped MBGNs and 5Zn-MBGNs had a comparable influence on cell viability, while it was enhanced by IDPs of 5Cu-MBGNs compared to the other MBGNs. IDPs of 5Cu-MBGNs had slightly positive effects on ECM formation and calcification. 5Zn-MBGNs provided the most favorable pro-osteogenic properties since they increased not only cellular osteogenic differentiation and ECM-related gene expression but also ECM formation and calcification significantly. Future studies should analyze other relevant properties of MBGNs, such as their impact on angiogenesis.

Cerium (Ce) is a promising candidate ion for application in bone tissue engineering (BTE) since it reduces the presence of reactive oxygen species. Ce-doped mesoporous bioactive glass nanoparticles (MBGNs) serving as vectors for the local application of Ce already demonstrated stimulating effects on the expression of pro-osteogenic genes in Saos-2 cells. So far, there is no evidence available about the effects of Ce-doped MBGNs on the viability, osteogenic differentiation and the formation of the osseous extracellular matrix (ECM) of primary human bone marrow-derived mesenchymal stromal cells (BMSCs). Therefore, in this study, the biocompatibility of the ionic dissolution products (IDPs) of MBGNs containing increasing concentrations of CeO ₂ (0.05 MCe-MBGNs, composition in mol%: 86.6SiO ₂ -12.1CaO-1.3CeO ₂ ; and 0.2 MCe-MBGNs, composition in mol%: 86.0SiO ₂ -11.8CaO-2.2CeO ₂ ) and unmodified MBGNs (composition in mol%: 86SiO ₂ -14CaO) was evaluated using human BMSCs. Eventually, the impact of the MBGNs’ IDPs on the cellular osteogenic differentiation and their ability to build and mature a primitive osseous ECM was assessed. The Ce-doped MBGNs had a positive influence on the viability and stimulated the cellular osteogenic differentiation of human BMSCs evaluated by analyzing the activity of alkaline phosphate as a marker enzyme for osteoblasts in the present setting. Furthermore, the formation and calcification of a primitive osseous ECM was significantly stimulated in the presence of Ce-doped MBGNs in a positive concentration-dependent manner as demonstrated by an elevated presence of collagen and increased ECM calcification. The results of this in-vitro study show that Ce-doped MBGNs are attractive candidates for further application in BTE.

An ICIE16-bioactive glass (BG) composition (in mol%: 49.5 SiO₂, 6.6 Na₂O, 36.3 CaO, 1.1 P₂O₅, and 6.6 K₂O) has demonstrated excellent in vitro cytocompatibility when cultured with human bone marrow-derived mesenchymal stromal cells (BMSCs). However, its impact on the development of an osseous extracellular matrix (ECM) is limited. Since zinc (Zn) is known to enhance ECM formation and maturation, two ICIE16-BG-based Zn-supplemented BG compositions, namely 1.5 Zn-BG and 3Zn-BG (in mol%: 49.5 SiO₂, 6.6 Na₂O, 34.8/33.3 CaO, 1.1 P₂O₅, 6.6 K₂O, and 1.5/3.0 ZnO) were developed, and their influence on BMSC viability, osteogenic differentiation, and ECM formation was assessed. Compared to ICIE16-BG, the Zn-doped BGs showed improved cytocompatibility and significantly enhanced osteogenic differentiation. The expression level of the osteopontin gene was significantly higher in the presence of Zn-doped BGs. A larger increase in collagen production was observed when the BMSCs were exposed to the Zn-doped BGs compared to that of the ICIE16-BG. The calcification of the ECM was increased by all the BG compositions; however, calcification was significantly enhanced by the Zn-doped BGs in the early stages of cultivation. Zn constitutes an attractive addition to ICIE16-BG, since it improves its ability to build and calcify an ECM. Future studies should assess whether these positive properties remain in an in vivo environment.